18-45727373-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015865.7(SLC14A1):c.-22+2360C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,550,130 control chromosomes in the GnomAD database, including 177,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14105 hom., cov: 33)
  • Exomes 𝑓: 0.48 (163733 hom.)
• Consequence: SLC14A1 NM_015865.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

Genes affected

SLC14A1 (HGNC:10918): (solute carrier family 14 member 1 (Kidd blood group)) The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 18-45727373-C-A is Benign according to our data. Variant chr18-45727373-C-A is described in ClinVar as [Benign]. Clinvar id is 3059256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A1	NM_015865.7	c.-22+2360C>A		intron_variant		ENST00000321925.9
LOC105372093	XR_935423.3	n.826+10093G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A1	ENST00000321925.9	c.-22+2360C>A		intron_variant		1	NM_015865.7	P1
	ENST00000589510.5	n.160+10093G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63095 AN: 152014 Hom.: 14107 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.441

GnomAD3 exomes AF: 0.472 AC: 72517 AN: 153612 Hom.: 17494 AF XY: 0.470 AC XY: 38287 AN XY: 81508

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.511

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.538

Gnomad SAS exome AF: 0.426

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.494

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.481 AC: 672907 AN: 1397998 Hom.: 163733 Cov.: 46 AF XY: 0.480 AC XY: 330635 AN XY: 689316

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.415 AC: 63104 AN: 152132 Hom.: 14105 Cov.: 33 AF XY: 0.414 AC XY: 30756 AN XY: 74354

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.440

Alfa AF: 0.453 Hom.: 7941

Bravo AF: 0.408

Asia WGS AF: 0.430 AC: 1500 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC14A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	17
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11877086; hg19: chr18-43307338; COSMIC: COSV58933785; COSMIC: COSV58933785;